BREAST-TUMOR XENOGRAFT TARGETING AND THERAPY STUDIES USING RADIOLABELED CHIMERIC ANTI-CEA MONOCLONAL-ANTIBODY T84.66

Abstract

Carcinoembryonic antigen (CEA) is expressed in approximately 60% of breast carcinomas. T84.66 is a well characterized anti-CEA murine monoclonal antibody (MAb) that does not cross-react with other CEA-related proteins. It has been humanized and used extensively after radiolabeling in clinical/experimental protocols for localization/therapy of colorectal cancer. MCF-7 human breast cancer cell line expresses CEA and is tumorigenic in athymic mice. In order to determine if anti-CEA MAb could specifically target breast cancer CEA, biodistribution, radiolocalization and therapy studies were performed in the animal model. Five tumor-bearing animals per time point were injected with 15 muCi of In-111-cT84.66. Mice were imaged and sacrificed at 24, 48, 72 and 144 h and biodistribution studies performed. For therapy studies, 19 tumor-bearing mice were injected either with 120 muCi of 90Y-cT84.66 or PBS. The tumors were measured tri-weekly and weighed at autopsy 21 days post therapy. Activity accumulation steadily increased in the tumors reaching 21% of the injected dose per gram of tumor (ID/g) at 144 h. At that time, the %ID/g in the tumor was 3 times higher than that in blood and the liver and 8 times higher than in other major organs. On day 10 post-therapy, 16 of the 19 control mice had tumor volumes between 1 and 3 cm3, while none of the treated tumors ever reached 1 cm3 in size. At autopsy, a 12-fold tumor weight difference (p=0.0001) was observed between control and treated mice (2.4g vs. 0.2g average weight, respectively). In summary, breast cancer CEA was specifically targeted with T84.66 allowing good tumor localization as well as significant tumor growth inhibition. Given the significant expression of CEA in breast cancer, this tumor should be included into the CEA-expressing malignancies for targeting with anti-CEA MAbs.